TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22855	68788;68789;68790	chr2:178577863;178577862;178577861	chr2:179442590;179442589;179442588
N2AB	21214	63865;63866;63867	chr2:178577863;178577862;178577861	chr2:179442590;179442589;179442588
N2A	20287	61084;61085;61086	chr2:178577863;178577862;178577861	chr2:179442590;179442589;179442588
N2B	13790	41593;41594;41595	chr2:178577863;178577862;178577861	chr2:179442590;179442589;179442588
Novex-1	13915	41968;41969;41970	chr2:178577863;178577862;178577861	chr2:179442590;179442589;179442588
Novex-2	13982	42169;42170;42171	chr2:178577863;178577862;178577861	chr2:179442590;179442589;179442588
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGG
• RefSeq wild type template codon: TCC
• Domain: Fn3-54
• Domain position: 15
• Structural Position: 17
• Q(SASA): 0.5056
• Predicted PPI site: N

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
R/K	None	None	0.025	N	0.233	0.124	0.226586394389	gnomAD-4.0.0	1.64144E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.93846E-06	0	0

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
R/A	0.7489	likely_pathogenic	0.7817	pathogenic	-0.694	Destabilizing	0.845	D	0.641	neutral	None	None	None	None	N
R/C	0.3638	ambiguous	0.3822	ambiguous	-0.608	Destabilizing	0.999	D	0.791	deleterious	None	None	None	None	N
R/D	0.9426	likely_pathogenic	0.9548	pathogenic	-0.416	Destabilizing	0.975	D	0.683	prob.neutral	None	None	None	None	N
R/E	0.7648	likely_pathogenic	0.7877	pathogenic	-0.357	Destabilizing	0.845	D	0.565	neutral	None	None	None	None	N
R/F	0.9574	likely_pathogenic	0.9601	pathogenic	-0.952	Destabilizing	0.996	D	0.753	deleterious	None	None	None	None	N
R/G	0.5893	likely_pathogenic	0.5969	pathogenic	-0.919	Destabilizing	0.892	D	0.615	neutral	N	0.482923433	None	None	N
R/H	0.2569	likely_benign	0.2766	benign	-1.268	Destabilizing	0.987	D	0.589	neutral	None	None	None	None	N
R/I	0.853	likely_pathogenic	0.8734	pathogenic	-0.115	Destabilizing	0.987	D	0.757	deleterious	None	None	None	None	N
R/K	0.1666	likely_benign	0.185	benign	-0.805	Destabilizing	0.025	N	0.233	neutral	N	0.424011203	None	None	N
R/L	0.7491	likely_pathogenic	0.7659	pathogenic	-0.115	Destabilizing	0.916	D	0.615	neutral	None	None	None	None	N
R/M	0.7806	likely_pathogenic	0.8126	pathogenic	-0.149	Destabilizing	0.999	D	0.615	neutral	N	0.501323097	None	None	N
R/N	0.8685	likely_pathogenic	0.9041	pathogenic	-0.226	Destabilizing	0.975	D	0.598	neutral	None	None	None	None	N
R/P	0.8821	likely_pathogenic	0.8857	pathogenic	-0.289	Destabilizing	0.987	D	0.711	prob.delet.	None	None	None	None	N
R/Q	0.2112	likely_benign	0.2235	benign	-0.546	Destabilizing	0.975	D	0.616	neutral	None	None	None	None	N
R/S	0.8269	likely_pathogenic	0.8509	pathogenic	-0.859	Destabilizing	0.892	D	0.649	neutral	N	0.483478007	None	None	N
R/T	0.776	likely_pathogenic	0.8154	pathogenic	-0.66	Destabilizing	0.967	D	0.628	neutral	N	0.464047723	None	None	N
R/V	0.868	likely_pathogenic	0.8863	pathogenic	-0.289	Destabilizing	0.975	D	0.729	prob.delet.	None	None	None	None	N
R/W	0.6345	likely_pathogenic	0.637	pathogenic	-0.746	Destabilizing	0.999	D	0.793	deleterious	N	0.507906463	None	None	N
R/Y	0.8427	likely_pathogenic	0.8606	pathogenic	-0.382	Destabilizing	0.996	D	0.717	prob.delet.	None	None	None	None	N

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.